Beta Agonis

Beta2 Adrenergic Agents –
Short-Acting Review
06/15/2009
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Beta2 Adrenergic Agents, Short-Acting Review
FDA-Approved Indications
Drug Name Manufacturer Reversible Prevention Chronic Age of
Bronchospasm of Obstructive Use
Exercise Pulmonary (years)
Prevention Relief
Induced Disease
and
Broncho- (COPD)
Treatment
spasm
Short-Acting Inhalation Agents
Proventil HFA® X X X >4
albuterol HFA MDI Schering
(Proventil HFA,
Ventolin HFA, Ventolin HFA®
ProAir HFA)1,2,3 GlaxoSmithKline
ProAir HFA®
Ivax
albuterol inhalation generic X 2-12
solution
(Accuneb®)4,5
levalbuterol Sepracor X >6
inhalation solution
(Xopenex®)6
levalbuterol HFA Sepracor X >4
MDI
(Xopenex® HFA)7
metaproterenol generic X X X >6
inhalation solution8
pirbuterol MDI 3M X >12
(Maxair®
Autohaler)9
Oral Agents
albuterol oral generic X >2
syrup10
albuterol oral generic X >6
tablets11
metaproterenol oral generic X X >6
syrup12
metaproterenol oral generic X >6
tablets13
terbutaline tablets14 generic X X >12
HFA=hydrofluroalkane; MDI=metered-dose inhaler
Overview
Beta2-agonist bronchodilators are used for the treatment and prevention of bronchospasm
associated with asthma, prophylaxis of exercise-induced bronchospasm (EIB), and in the
treatment of chronic obstructive pulmonary disease (COPD).
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Beta2 Adrenergic Agents, Short-Acting
Asthma
Short-acting beta2-agonists have not been shown to be as beneficial as controller medications for
asthma management, but due to their rapid onset, they are useful for temporary relief of
bronchoconstriction and the accompanying acute symptoms such as wheezing, chest tightness,
and cough.15
The 2007 guidelines from the National Heart Lung and Blood Institute recommend that for
patients over age five years with moderate persistent asthma or asthma not controlled by low-
dose corticosteroids that consideration be given for use of a combination of inhaled
corticosteroids and long acting beta2-agonists or for increasing the dose of inhaled
corticosteroids. For patients with severe persistent asthma, a combination of a long acting
beta2-agonist and an inhaled corticosteroid is recommended. For exercise-induced
bronchospasm, long acting beta2-agonists may be used for prevention; however, it is noted that
frequent or chronic use may disguise poorly controlled persistent asthma.
In November 2007, the National Asthma Education and Prevention Panel released a summary of
the third report of the Expert Panel (EPR-3) that emphasizes the importance of asthma control
and identifies asthma severity as the intrinsic intensity of the disease process. The
recommendation from EPR-3 is to assess severity to initiate therapy and assess control to adjust
therapy in patients as young as five years of age.
In 2007, the Global Initiative for Asthma (GINA) guidelines for asthma management were
updated to reflect a change in focus from asthma severity to asthma control.16 Asthma control
is defined as no or minimal daytime symptoms; no limitations of activity; no nocturnal symptoms;
no or minimal need for rescue medications; normal or near normal lung function; and no
exacerbations. A five-step treatment approach is discussed in these guidelines that offer
flexibility to step up treatment when asthma is uncontrolled or step down treatment when
asthma is controlled. These guidelines suggest treatment with short-acting beta-2 agonists only
on an as-needed basis particularly if patients experience only occasional daytime symptoms of
short duration. When symptoms are more frequent and/or worsen periodically, patients require
regular controller therapy.
In 2008, the GINA guidelines were further updated to produce a more streamlined, user-friendly
document that emphasizes the importance of asthma control with appropriate treatment. The
asthma classification system is defined as three levels of control: controlled, partly controlled, or
uncontrolled. Roles of other medications used to treat asthma (e.g. leukotriene modifiers, long
acting beta-agonists, cromones and inhaled glucocorticoids) have evolved since prior versions
of the guidelines and have been included in the 2008 update.17
COPD
Bronchodilator medications are central to the symptomatic management of COPD.18,19,20,21 They

improve emptying of the lungs, tend to reduce dynamic hyperinflation at rest and during exercise,
and improve exercise performance. 22 They are given either on an as-needed basis for relief of
persistent or worsening symptoms or on a regular basis to prevent or reduce symptoms. Regular
bronchodilation with these drugs does not modify the decline of function in mild COPD or the
prognosis of the disease.23 The principal bronchodilator treatments are beta2-agonists,
anticholinergics, and theophylline. These may be given either as monotherapy or preferably, in
combination with the inhaled agents. While short-acting beta2-agonists can be used on an as-
needed basis in mild COPD, regular treatment with a long acting agent is required as the disease
progresses.24
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In January 2008, the updated Global Initiative for chronic obstructive Lung Disease (GOLD)
guidelines were released and state that beta2-agonist bronchodilators are among the principal
treatments for symptomatic management of COPD.25 The guidelines also state that regular
treatment with long-acting bronchodilators is more effective and convenient than treatment with
short-acting bronchodilators.
In 2005, the American College of Chest Physicians (ACCP) and the American College of
Allergy, Asthma, and Immunology (ACAAI) issued joint evidence-based guidelines for selecting
aerosol delivery devices for use in asthma or COPD.26 The authors performed a systematic
review of randomized controlled trials comparing the efficacy and adverse effects of treatment
using nebulizers versus pressurized MDIs with or without a spacer/holding chamber versus
DPIs as delivery systems for beta2-agonists, anticholinergic agents, and corticosteroids in
several commonly encountered clinical settings and patient populations. The authors conclude
that devices used for the delivery of bronchodilators and steroids can be equally efficacious.
Pharmacology
Beta-agonists stimulate adenyl cyclase, the enzyme that catalyzes the formation of cyclic-3'5'
adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). Increased cyclic
AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release
of mediators of immediate hypersensitivity, especially from mast cells. Beta2-agonists relieve
reversible bronchospasm by relaxing the smooth muscles of the bronchioles in conditions
associated with asthma, COPD, or bronchiectasis. Bronchodilation may additionally facilitate
expectoration.
Although there are both beta1 and beta2 receptors in the heart, the latter are more predominant
in the lungs, where they serve as the primary adrenergic receptors in bronchial smooth muscle.
In order to reduce cardiac toxicities (e.g., tachyarrhythmias), the use of beta2 specific agonists
is preferred in the treatment of bronchospasm. This has minimized the use of less specific and
less safe agents such as epinephrine (Primatene Mist®) and isoproterenol (Isuprel®). To further
reduce cardiac toxicities, non-systemic dosage forms given by inhalation are preferred to oral
dosage forms.
Since the signing of the Montreal Protocol in 1987, new propellants, such as hydrofluoroalkane
(HFA), for use in pressurized metered-dose inhalers that are non-ozone-depleting have been
developed. Several randomized, double-blind, placebo-controlled, crossover studies have
shown that albuterol MDI pressurized by HFA are equivalent, in terms of efficacy and
tolerability, to the original chlorofluorocarbon (CFC) albuterol MDI in both adolescents and
adults.27,28,29,30 This equivalence was shown for both the treatment and prophylactic (EIB)
indications of albuterol. The reformulation effort is underway for the CFC containing products.
The FDA completed its phase-out of albuterol inhalers using ozone-depleting CFCs as
propellants on December 31, 2008. Patients who used albuterol inhalers containing CFCs were
switched to alternative inhalers that contain a propellant called hydrofluoroalkane (HFA).
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Pharmacokinetics
Drug Relative ß2 Onset of Action Duration of Action
Specificity (minutes) (hours)
albuterol HFA MDI (ProAir HFA, ß2 >> ß1 5.4-8.2 3-6
Proventil HFA, Ventolin HFA)31,32,33
albuterol inhalation solution ß2 >> ß1 5-15 3-6
34,35
(generic, Accuneb)
levalbuterol inhalation solution ß2 >> ß1 10-17 5-8
(Xopenex)36
levalbuterol HFA MDI ß2 >> ß1 5-10 3-6
37
(Xopenex HFA)
metaproterenol inhalation solution38 ß2 > ß1 5-30 2-6
39
pirbuterol MDI (Maxair) ß2 > ß1 <5 5
Oral Agents
albuterol syrup, tablets40,41 ß2 >> ß1 30 4-8
metaproterenol syrup, tablets42 ß2 > ß1 30 >4
terbutaline tablet43 ß2 >> ß1 30 4-8
Contraindications/Warnings44,45,46,47,48,49,50,51,52
No specific contraindications exist for the short-acting beta-agonists.
Warnings that are common to the short-acting beta-agonists include: paradoxical bronchospasm
(can be life threatening), cardiovascular effects (e.g. effects on blood pressure and pulse rate),
excessive dose and usage, acute deterioration of asthma and use of anti-inflammatory agents
(e.g. corticosteroids). Short-acting beta-agonists should be used with caution in patients with
heart disease, seizure disorder, diabetes and hyperthyroidism.
There have been rare reports of seizures in patients receiving terbutaline; seizures did not recur
in these patients after the drug was discontinued.
Drug Interactions53,54,55,56,57,58,59,60,61,62
Monoamine Oxidase (MAO) Inhibitors and Tricyclic Antidepressants
All beta2-agonists should be administered with extreme caution to patients being treated with
MAO inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because
these agents may potentiate the action of adrenergic agonists on the cardiovascular system.
Allow two weeks after discontinuation of MAO inhibitors before initiating therapy with agents in
this category.
Beta-Adrenergic Receptor Blocking Agents
Beta-blockers not only block the pulmonary effect of beta-agonists but may also produce severe
bronchospasm in patients with asthma or COPD. Therefore, patients with asthma or COPD
should not normally be treated with beta-blockers. However, under certain circumstances, such
as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of
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beta-adrenergic blocking agents in patients with asthma or COPD. In this setting,

cardioselective beta-blockers could be considered, although they should be administered with
caution.
Diuretics
The ECG changes and/or hypokalemia that may result from the administration of non-
potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by
beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Although the clinical significance of these effects is not known, caution is advised in the
coadministration of beta-agonists with non-potassium-sparing diuretics. Concomitant treatment
with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of
adrenergic agonists.
Digoxin
Mean decreases of 16 and 22 percent in serum digoxin levels were demonstrated after single-
dose intravenous and oral administration of recemic albuterol, respectively, to normal volunteers
who had received digoxin for ten days. The clinical significance of these findings for patients
with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is
unclear; nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in
patients who are currently receiving digoxin and albuterol and levalbuterol.
Adverse Effects
Drug Headache Nausea/ Nervousness Palpitations Tachycardia Tremor
Vomiting

albuterol HFA MDI (Proventil 7-20 7 - 10 7 <3 <3 - 7 2-7
HFA, Ventolin HFA, ProAir
HFA)63,64,65
albuterol inhalation solution nr 1.7 and reported reported nr reported
66,67
(generic, Accuneb) .9
levalbuterol inhalation 7.6 - 11.9 <2 2.8 - 9.6 reported 2.7 - 2.8 0 - 6.8
solution (Xopenex)68
levalbuterol HFA MDI reported 10.5 reported reported reported reported
69
(Xopenex HFA)
metaproterenol inhalation 3.3 7.7 - 14 14.1 <1 2.5 – 16.6 2.5 – 33
solution70
pirbuterol MDI (Maxair)71 1.3 1.3 4.5 1.3 1.3 1.3
Oral Agents
albuterol syrup72 4 <1 - 2 9 - 15 <1 1-2 10
albuterol tablets73 7 2 20 5 5 20
74
metaproterenol syrup 1.1 1.3 4.8 <1 6.1 1.6
75
metaproterenol tablets 7 0.8 - 3.6 20.2 3.8 17.1 16.9
terbutaline tablets76 7.8 - 10 1.3 - 10 <5 - 31 <23 1.3 - 3 <5 – 38
Adverse effects data are reported as a percentage. Adverse effects data are obtained from package
inserts and are not meant to be comparative. nr = not reported.
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Special Populations77,78,79,80,81,82,83,84,85
Pediatrics
Most of the short-acting beta-agonists have been studied in pediatric patients and shown to be
safe and effective in adults and children as young as two years of age. Important to note is that
the safety and effectiveness of pirbuterol (Maxair) in children has not been proven. There is
insufficient clinical data to establish safety and efficacy of terbutaline sulfate therefore, it is not
recommended for patients under the age of 12 years.
Pregnancy
There are no adequate and well-controlled studies of these agents in pregnant women.
Terbutaline is Pregnancy Category B. All of the short-acting beta-agonists are Pregnancy
Category C. They should only be used during pregnancy if the potential benefit justifies the
potential risk.
Other considerations – renal, hepatic, race, etc.
These agents have not been studied in a geriatric population. Special caution should be
observed when using these agents in elderly patients with coexisting conditions like impaired
renal function and cardiovascular disease that could be adversely affected by this class of drug.
No dosage adjustments needed in the hepatically impaired patients who use albuterol, albuterol
HFA, pirbuterol, and levalbuterol.
Exercise caution and monitor the renally impaired who use albuterol, albuterol HFA, pirbuterol,
levalbuterol. No special monitoring or dosage adjustments are needed in the renally impaired
patients who use metaproterenol.
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Dosages
Drug Usual Adult Dosage Usual Pediatric Availability
Dose
albuterol HFA MDI 2 inhalations 2 inhalations every 90 mcg per actuation
(Proventil HFA, Ventolin every 4-6 hrs as 4-6 hrs as needed
HFA, ProAir HFA)86,87,88 needed
Prevention of EIB: 2 Prevention of EIB:
inhalations 15-30 2 inhalations 15-30
minutes prior to minutes prior to
exercise exercise
albuterol inhalation 2.5 mg every 6-8 hrs 0.63-2.5 mg three generic:
solution as needed to four times daily 2.5 mg/3 mL,
(generic, Accuneb)89,90 as needed 5 mg/mL
Accuneb or low-dose
generic:
0.63 mg/3 mL,
1.25 mg/3 mL
levalbuterol inhalation 0.63-1.25 mg 0.31-0.63 mg three 0.31 mg/3 mL,
solution (Xopenex)91 three times daily times daily 0.63 mg/3 mL,
1.25 mg/3 mL
levalbuterol HFA MDI 2 inhalations every 2 inhalations every 45 mcg per actuation
(Xopenex HFA)92 4-6 hrs as needed 4-6 hrs as needed
metaproterenol inhalation 10-15 mg three to four 5-10 mg three to 8 mg/2 mL,
solution93 times daily four times daily 5 mg/mL,
12 mg/2 mL,
pirbuterol MDI (Maxair)94 2 inhalations every 4-6 -- 200 mcg per actuation
hrs. Not to exceed 12
inhalations per day.
Oral Agents
albuterol oral syrup95 2-4 mg every 6-8 hrs 0.1-0.2 mg/kg 2 mg/5 mL
every 8 hrs
albuterol oral tablets96 2-4 mg every 6-8 hrs 2 mg every 6-8 hrs 2 mg, 4 mg
metaproterenol oral 20 mg three to four 10 mg three to four 10 mg/5 mL
syrup97 times daily times daily
metaproterenol oral 20 mg three to four Age 6 – 9 yo or 10 mg, 20 mg
tablets98 times daily weight < 60lbs:
10 mg three to four
times daily
Age > 9yo or
weight > 60lbs:
20 mg three to four
times daily
terbutaline tablets99 2.5-5 mg three times 2.5 mg three times 2.5 mg, 5 mg
daily daily
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Clinical Trials
Search Strategy
Articles were identified through searches performed on PubMed and review of information sent
by manufacturers. Search strategy included the use of all drugs in this class. Randomized,
controlled, comparative trials are considered the most relevant in this category. Studies included
for analysis in the review were published in English, performed with human participants and
randomly allocated participants to comparison groups. In addition, studies must contain clearly
stated, predetermined outcome measure(s) of known or probable clinical importance, use data
analysis techniques consistent with the study question and include follow-up (endpoint
assessment) of at least 80 percent of participants entering the investigation. Despite some
inherent bias found in all studies including those sponsored and/or funded by pharmaceutical
manufacturers, the studies in this therapeutic class review were determined to have results or
conclusions that do not suggest systematic error in their experimental study design. While the
potential influence of manufacturer sponsorship/funding must be considered, the studies in this
review have also been evaluated for validity and importance.
ASTHMA
albuterol MDI (Proventil, Ventolin) versus formoterol DPI (Foradil)
Formoterol DPI 12 mcg or 24 mcg twice daily was compared to albuterol MDI 180 mcg four
times daily and placebo in a total of 541 patients with mild-to-moderate asthma in a twelve-
week, multicenter, randomized, double-blind, parallel-group study.100 At all measured time
points during the 12 hours after the first dose, mean percentages of predicted FEV1 values for
formoterol and albuterol groups were significantly higher than those for the placebo group
(p≤0.037). Formoterol, 12 mcg and 24 mcg were associated with a significantly higher
percentage of predicted FEV1 values than albuterol (p≤0.018 and p ≤.00,1 respectively) at hours
four through six and at hour 12. The percentages of predicted FEV1 values for albuterol were
significantly greater than those for formoterol, 12 mg (p≤0.027) at five minutes through 60
minutes, and at hours seven and eight.
A study compared the efficacy and tolerability of formoterol DPI 12 mcg and 24 mcg twice daily
with albuterol MDI 180 mcg four times daily and placebo.101 A total of 554 adolescents and
adults (ages 12-75 years) with mild to moderate asthma were randomized to the four treatment
groups, of which 484 patients completed the 12-week, multicenter, double-blind, double-dummy,
placebo-controlled, parallel-group study. For the primary efficacy variable, FEV1, both
formoterol DPI 12 and 24 mcg were statistically superior to placebo at all time points on all test
days (p<0.017) and to albuterol MDI at most time points on all test days (p<0.001). The onset
of improvement in FEV1 was rapid with 15 percent increase within five minutes in 57, 71, and 65
percent of formoterol DPI 12 mcg, formoterol DPI 24 mcg, and albuterol MDI patients,
respectively. Formoterol DPI was also showed greater improvement to placebo and albuterol
MDI in terms of secondary efficacy variables: AUC, percentage of predicted FEV1, forced vital
capacity (FVC), asthma symptom scores, and peak expiratory flow rate (PEFR). Formoterol
DPI and albuterol MDI were both well-tolerated.
Eighteen patients with EIB were randomized in a double-blind, placebo-controlled, four-way,

crossover study.102 Each patient received, in random sequence, a single dose of formoterol DPI
12 or 24 mcg, albuterol MDI 180 mcg, or placebo at intervals of three to seven days. Pulmonary
function measurements were taken before and after exercise challenge tests at 15 minutes
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postdose and at four, eight, and 12 hours postdose. Both doses of formoterol DPI produced
significantly greater protection against EIB than placebo at all time points (p<0.016). The two
doses of formoterol DPI were not significantly different from one another at any time. Protection
against EIB with albuterol MDI was clinically significant only at the 15 minute postdose time
point and was statistically superior to placebo at 15 minutes and four hours. Rescue medication
was used substantially less with either dose of formoterol DPI, compared with albuterol MDI or
placebo. All treatments were well tolerated. Two-hour postdose electrocardiograms (ECGs)
and vital signs were unremarkable for all study treatments.
In a double-dummy, four-way, crossover study, 20 adult and adolescent asthmatic patients

received single doses of formoterol DPI 12 and 24 mcg, albuterol MDI 180 mcg, and placebo.103
Exercise challenge tests were conducted at 15 minutes and at four, eight, and 12 hours
postdose. Of the 20 patients who were enrolled, 17 patients completed the study. Compared
with placebo, both doses of formoterol DPI produced significantly greater inhibition of FEV1
decreases at all time points (p<0.01). There were no significant differences in efficacy
measures between the two formoterol DPI doses throughout the study. The exercise-induced
decrease in FEV1 after albuterol MDI treatment was significantly reduced compared with
placebo only at 15 minutes after dosing (p<0.05). Formoterol DPI and albuterol MDI exhibited a
similar rapid onset of action (<15 minutes), but formoterol DPI continued to protect patients
against EIB for at least 12 hours (p<0.01), whereas albuterol MDI was no longer clinically
effective by the four hour exercise challenge test.
albuterol inhalation solution (Proventil, Ventolin) versus levalbuterol inhalation solution

(Xopenex)
In a randomized, double-blind, placebo-controlled, crossover study, 20 adults with mild to

moderate asthma received single doses of levalbuterol inhalation solution (0.31, 0.63, and 1.25
mg) and albuterol inhalation solution (2.5 mg).104 All doses of active treatment produced a
significantly greater degree of bronchodilation (measured by change in FEV1) than placebo, and
there were no significant differences between any of the active treatment arms. The
bronchodilator response of levalbuterol 1.25 mg and albuterol 2.5 mg were clinically comparable
over the six hour evaluation period, except for a slightly longer duration of action after
administration of levalbuterol 1.25 mg. Systemic beta adrenergic adverse effects were
observed with all active doses. Levalbuterol 1.25 mg produced a slightly higher rate of systemic
beta adrenergic adverse effects than the albuterol 2.5 mg dose.
A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in

338 children with mild to moderate asthma.105 Following a one week placebo run-in period,
subjects were randomized to nebulized levalbuterol 0.31 or 0.63 mg, albuterol 1.25 or 2.5 mg, or
placebo given three times daily for three weeks. Of the 338 patients who were randomized, 316
patients completed the study. Efficacy, measured by mean peak change in FEV1, was
demonstrated for all active treatment regimens compared with placebo. The onset and duration
of effect of levalbuterol were clinically comparable to those of albuterol.
A randomized, double-blind, controlled trial was conducted in children age one to 18 years
(n=482) in the emergency department (ED) and inpatient asthma care unit of an urban tertiary
children's hospital.106 Patients received a nebulized solution of either 2.5 mg racemic albuterol
or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the
asthma care unit were treated in a standardized fashion by using the same blinded drug
assigned in the ED. Hospitalization rate was the primary outcome. Hospitalization rate was
significantly lower in the levalbuterol group (36 percent) than in the racemic albuterol group (45
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percent, p=0.02). The adjusted relative risk of admission in the racemic group compared with
the levalbuterol group was 1.25 (95% confidence interval (CI), 1.01 - 1.57). Hospital length of
stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic
albuterol, 50.3 hours; p=0.63). No significant adverse events occurred in either group.
COPD
albuterol MDI (Proventil, Ventolin) versus formoterol DPI (Foradil) versus salmeterol DPI
(Serevent) in COPD
A cross-over, randomized, double-blind, placebo-controlled study was carried out on 20 COPD

patients.107 Patients underwent pulmonary function testing and dyspnea evaluation in basal
condition and five, 15, 30, 60 and 120 minutes after bronchodilator (albuterol MDI, formoterol
DPI, or salmeterol DPI) or placebo administration. The results indicated that in COPD patients
with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory
capacity after bronchodilator administration, which correlated closely with the improvement of
dyspnea sensation at rest. On average, formoterol DPI elicited the greatest increase in
inspiratory capacity than the other bronchodilators used, though the difference was significant
only with salmeterol DPI.
Meta Analyses
A systematic review of pertinent randomized, controlled, clinical trials was undertaken using
MEDLINE, EmBase, and the Cochrane Library databases to determine if a difference in efficacy
and adverse effects exists among the various aerosol delivery devices (MDI versus DPI versus
nebulizers) used in the management of asthma and COPD exacerbations.108 A total of 254
outcomes were tabulated. Of the 131 studies that met the eligibility criteria, only 59 (primarily
those that tested beta2-agonists) proved to have useable data. None of the pooled meta-
analyses showed a significant difference among devices in any efficacy outcome in any patient
group for each of the clinical settings that were investigated. The adverse effects that were
reported were minimal and were related to the increased drug dose that was delivered. Each of
the delivery devices provided similar outcomes in patients using the correct technique for
inhalation.
Summary
Due to its rapid onset of action, relative lack of adverse systemic effects, and availability of
multiple dosage forms, albuterol remains the most commonly used short-acting beta2-agonist
bronchodilator. Albuterol CFC MDIs are no longer available as of December 31, 2008.
Schering (Proventil HFA), Ivax (ProAir HFA) and GlaxoSmithKline (Ventolin HFA) produce
albuterol inhalers using HFA propellant.
In general, oral dosage forms of albuterol are less utilized than the inhaled forms due to
systemic beta-adrenergic stimulation of the former, especially in patients sensitive to these
effects, such as those with cardiovascular disease. Metaproterenol is neither as beta2 selective
nor as long acting as albuterol, therefore should not be considered for first-line therapy. Another
beta2-agonist, terbutaline, is more beta2 selective than metaproterenol but is available only as
oral tablets. The short duration of action of terbutaline reduces its value in the treatment of
bronchoconstriction.
Levalbuterol (Xopenex) is the R-enantiomer form of albuterol. Levalbuterol (Xopenex)
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inhalation solution has similar efficacy to albuterol inhalation solution when given in equivalent
doses. In addition, an HFA-propelled inhaler containing the enantiomer of albuterol is available
as levalbuterol HFA (Xopenex HFA). There are no significant differences in adverse effects
between albuterol and levalbuterol formulations.
References
1
Proventil HFA [package insert]. Kenilworth, NJ; Key Pharmaceuticals; November 2007.
2
Ventolin HFA [package insert]. Research Triangle Park, NC; GlaxoSmithKline; April 2008.
3
ProAir HFA [package insert]. Miami, FL; Ivax; September 2008.
4
Proventil Inhalation Solution [package insert]. Kenilworth, NJ; Schering Corporation; February 2002.
5
AccuNeb [package insert]. Napa, CA; Dey L.P.; January 2007.
6
Xopenex [package insert]. Marlborough, NH; Sepracor Inc; August 2007.
7
Xopenex HFA [package insert]. Marlborough, NH; Sepracor Inc. September 2005.
8
Alupent [package insert]. Ridgefield, CT; Boehringer Ingelheim Pharmaceuticals; July 2001.
9
Maxair [package insert]. Northridge, CA; 3M Pharmaceuticals;January 2008.
10
Proventil Syrup [package insert]. Kenilworth, NJ; Schering Corporation; June 1997.
11
Proventil Repetabs [package insert]. Kenilworth, NJ; Schering Corporation; October 2000.
12
13
14
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Bronchodilator medications are central to the symptomatic management of COPD.18,19,20,21 They

albuterol syrup, tablets40,41 ß2 >> ß1 30 4-8

metaproterenol syrup, tablets42 ß2 > ß1 30 >4

terbutaline tablet43 ß2 >> ß1 30 4-8

beta-adrenergic blocking agents in patients with asthma or COPD. In this setting,

Short-Acting Inhalation Agents

albuterol syrup72 4 <1 - 2 9 - 15 <1 1-2 10

terbutaline tablets76 7.8 - 10 1.3 - 10 <5 - 31 <23 1.3 - 3 <5 – 38

albuterol MDI (Proventil, Ventolin) versus formoterol DPI (Foradil)

Eighteen patients with EIB were randomized in a double-blind, placebo-controlled, four-way,

In a double-dummy, four-way, crossover study, 20 adult and adolescent asthmatic patients

albuterol inhalation solution (Proventil, Ventolin) versus levalbuterol inhalation solution

In a randomized, double-blind, placebo-controlled, crossover study, 20 adults with mild to

A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in

A cross-over, randomized, double-blind, placebo-controlled study was carried out on 20 COPD

Levalbuterol (Xopenex) is the R-enantiomer form of albuterol. Levalbuterol (Xopenex)

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